Lymphomagenesis:
Mechanisms and
Targeting
Arbeitsgruppe Dr. med. Bogner
Research Interests
Our laboratory is interested in the molecular processes that underlie tumorigenesis, tumor progression and tumor maintenance of malignant lymphoma.
Over the last decade, the incidence of indolent lymphoma is constantly increasing and the diseases remains incurable by conventional therapies. In contrast to aggressive lymphoma, the oncogenic events which drive the development of indolent lymphomas are little understood and remain elusive for most entities. However, prolonged cell survival ascribed to an imbalance of pro- and antiapoptotic proteins is a hallmark of most low-grade lymphomas, such as follicular lymphoma and chronic lymphocytic leukemia (CLL).
The overexpression of the anti-apoptotic protein Bcl-2 is a common feature in both lymphomas and embedded in the translocation of chromosome 14;18. In addition, aberrant signalling through surface receptors, such as the B-cell receptor and CD40, cooperate with genetic alterations and sustain tumor cell survival. One focus of our work is to disentangle the aberrant signalling pathways which lead to the de-regulation and modulation of apoptosis proteins. We are currently investigating the integration of innate into adaptive immune responses in ZAP-70-positive chronic lymphocytic leukemia and the impact on induction of programmed cell death or survival. Our work is dedicated not only to understand the pathogenesis of lymphomas, but also to help to invent new therapies for B-cell malignancies.
Another focus of our work is signalling pathways used in the communication between the tumor cell microenvironment and the malignant cell itself. It is tempting to speculate that the tumor cells themselves harness bystander cells to support their survival. Understanding how and when malignant B-cells and stromal cells interact will allow interference and offers a new approach to treat indolent lymphomas. In particular, we are interested how signalling through integrins is linked to defects in the apoptotic machinery. In addition, we investigate how the microenvironment is modulated by tumor cells and if interference with this modulation can be used as a new treatment strategy for lymphoma patients.
Bogner C, Kale J, Chi X , Shamas-Din A, Fradin C, Leber B and Andrews D. Currently under Review at Molecular Cell. Allosteric regulation of BH3 proteins in Bcl-XL complexes confers switch-like activation of Bax.
Wagner M, Oelsner M, Moore A, Götte F, Kuhn PH, Haferlach T, Fiegl M, Bogner C, Baxter EJ, Peschel C, Follows GA, Ringshausen I. Blood. 2016 Jan 28;127(4):436-48. doi: 10.1182/blood-2015-05-646935. Epub 2015 Oct 27. Integration of innate into adaptive immune responses in ZAP-70-positive chronic lymphocytic leukemia.
Bogner C, Leber B, Andrews DW. Curr Opin Cell Biol. 2010 Dec;22(6):845-51. Epub 2010 Aug 26. Apoptosis: embedded in membranes.
zum Büschenfelde CM, Wagner M, Lutzny G, Oelsner M, Feuerstacke Y, Decker T, Bogner C, Peschel C, Ringshausen I. Leukemia. 2010 Jan;24(1):141-52. doi: 10.1038/leu.2009.216. Epub 2009 Nov 12.
Recruitment of PKC-betaII to lipid rafts mediates apoptosis-resistance in chronic lymphocytic leukemia expressing ZAP-70.
Bogner C, Dechow T, Ringshausen I, Wagner M, Oelsner M, Lutzny G, Licht T, Peschel C, Pastan I, Kreitman RJ, Decker T. Br J Haematol. 2010 Jan;148(1):99-109. Epub 2009 Oct 11. Immunotoxin BL22 induces apoptosis in mantle cell lymphoma (MCL) cells dependent on Bcl-2 expression.
Ringshausen I, Oelsner M, Bogner C, Peschel C, Decker T. The immunomodulatory drug Leflunomide inhibits cell cycle progression of B-CLL cells. Leukemia. 2008 Mar;22(3):635-8
Bogner C, Peschel C, and Decker T. Leukemia & Lymphoma, February 2006; 47(2): 195 – 205. Targeting the proteasome in mantle cell lymphoma: a promising therapeutic approach.
Bogner C, Michael Sandherr, Michael Perker, Katrin Weick, Ingo Ringshausen, Christian Peschel and Thomas Decker. Ann Hematol, 2006, 2 DOI 10.1007/s00277-005- 0076-y Cyclin E but not bcl-2, bax or mcl-1 is differentially expressed in ZAP 70 positive and negative CLL cells.
Bogner C, Schneller F, Hipp S, Ringshausen I, Peschel C, and Decker T. Exp Hematol 31 (2003) 218-225 Cycling CLL cells are highly susceptible to inhibition of the proteasome: Involvement of p27, early D-type cyclins, Bax, and caspase- dependent and - independent pathways.
Bogner C, Ringshausen I, Schneller F, Fend F, Quintanilla-Martinez L, Häcker G, Peschel C, and Decker T. British Journal of Hematology 122 (2003) 260–268 Inhibition of the proteasome induces cell cycle arrest and apoptosis in Mantle cell lymphoma cells.
Decker T, Hipp S, Ringshausen I, Bogner C, Oelsner M, Schneller F, Peschel C. Rapamycin-induced G1 arrest in cycling B-CLL cells is associated with reduced expression of cyclin D3, cyclin E, cyclin A, and survivin. Blood 2003 Jan 1;101(1):278-85
Ringshausen I, Schneller F, Bogner C, Hipp S, Duyster J, Peschel C, Decker T. Constitutively activated phosphatidylinositol-3 kinase (PI-3K) is involved in the defect of apoptosis in B-CLL: association with protein kinase Cdelta. Blood 2002 Nov 15;100(10):3741-8
Mangolini M, Götte F, Moore A, Ammon T, Oelsner M, Lutzny-Geier G, Klein-Hitpass L, Williamson JC, Lehner PJ, Dürig J, Möllmann M, Rásó-Barnett L, Hughes K, Santoro A, Méndez-Ferrer S, Oostendorp RAJ, Zimber-Strobl U, Peschel C, Hodson DJ, Schmidt-Supprian M, Ringshausen I. Notch2 controls non-autonomous Wnt-signalling in chronic lymphocytic leukaemia. Nat Commun. 2018 Sep 21;9(1):3839. doi: 10.1038/s41467-018-06069-5.
Application
Written applications including CV are welcome and should be forwarded by e-mail to Dr. Christian Bogner.